Manhattan Isotope Starts Formal Process to Produce Sr-82

August 27, 2012 — Positron Corp., a molecular imaging healthcare company, announced the submission of a drug master file (DMF) with the U.S. Food and Drug Administration (FDA) for the production of active pharmaceutical ingredient (API)-grade strontium-82 (Sr-82) through its wholly owned subsidiary, Manhattan Isotope Technology LLC (MIT). This will offer a second source for the nuclear myocardial perfusion cardiac imaging agent.

A DMF is a document submitted to the FDA that contains complete information on an API or finished drug dosage form. The DMF contains factual and complete information on a drug product's chemistry, manufacturer, stability, purity, impurity profile, packaging and the cGMP status of any human drug product. The main objective of the DMF is to support regulatory requirements and to prove the quality, safety and efficacy of the medicinal product.

Manhattan Isotope’s DMF submission initiates the protocol, procedures and compliance required to produce Sr-82 for radiopharmaceutical applications, specifically for commercial use in Sr-82/Rubidium (Rb)-82 generators. Sr-82/Rb-82 generator manufacturers may now qualify MIT as a supply source and vendor for API grade Sr-82.

Manhattan Isotope’s DMF positions the company as the only commercial entity in the United States in the Sr-82 processing and production arena. Currently, the U.S. Department of Energy (DOE) is the only domestic supplier for many of the more than 300 different isotopes, which are critical in medical, commercial, research and national security applications. Recent shortages have emphasized the importance of managing the demand for critical isotopes.

“Our submission of the DMF is a very significant milestone, as it signifies Positron’s evolution towards a vertically integrated nuclear medicine healthcare company," said Jason Kitten, president of MIT. "Positron, through MIT, is the first private entity to demonstrate the expertise and ability to enter the market as a processor and supplier of API-grade strontium-82. Proficiencies in this segment are key to our end-to-end solution strategy. Positron’s ability to supply strontium and support production needs will not only stabilize the source supply of strontium-82, but will also lend growth to and strengthen the cardiac positron emission tomography (PET) market as a whole.”

PET images (MIP 0-60 min) of three Cynomolgus monkeys. Strong signals are detected at the sites where inserted catheters had roughened surfaces. Almost no other background signal is visible. Only accumulation in the gallbladder becomes visible at the bottom of the image. Credit: Piramal Imaging GmbH, Berlin Germany.

Note the high uptake of Ga-68-pentixafor on multi-planar reconstructions in the organs expressing CXCR4 such as the spleen (red arrows) and adrenal glands (yellow arrows), which was nearly completely blocked by the pre-injection of AMD 3100, a potent CXCR4 inhibitor. Strong accumulation of Ga-68-pentixafor was also found in the kidneys (asterisks) reflecting the renal clearance of the tracer. In addition, high, focal activities were detected in the abdominal aorta (red arrowheads) and right carotid artery (orange arrowheads) of atherosclerotic rabbits, whereas no significant signal could be detected in the non-injured left carotid artery (white arrowheads) of atherosclerotic and control rabbits, as well as in the abdominal aorta and right carotid artery of control rabbits. Furthermore, focal activities detected with PET in atherosclerotic plaques of the abdominal aorta and the right carotid artery decreased significantly when the same rabbit was re-imaged after blocking CXCR4 receptors. Image courtesy of Fabien Hyafil, M.D., Ph.D., Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany

A PET-CT cardiac perfusion exam from a Siemens Biograph scanner. The black and white areas of the image show the CT imaging of the anatomy. The colored portion shows the PET overlay on the myocardium and is color-coded to show tracer uptake values. This can show areas of the heart muscle where there are perfusion defects cause by infarcts or coronary artery blockages due to a heart attack and help determine the severity of the ischemia.

The whole body of a rat can be imaged for blood clots with one PET scan (which is overlaid here on an MRI image) using the FBP8 probe. Arrow points to a blood clot. Image courtesy of Peter Caravan, Ph.D.